Formation, elimination and remodeling of excitatory synapses on dendritic spines represent a continuous process that shapes the organization of synaptic networks during development. The molecular mechanisms controlling dendritic spine formation and stabilization therefore critically determine the rules of network selectivity. Recent studies have identified new molecules, such as Ephrins and Telencephalin that regulate filopodia motility and their transformation into dendritic spines. Trans-synaptic signaling involving nitric oxide, protease, adhesion molecules and Rho GTPases further controls contact formation or the structural remodeling of spines and their stability. Evidence also suggests that activity and induction of plasticity participate to the selection of persistent spines. Together these new data provide a better understanding of the mechanisms, speed and steps leading to the establishment of a stable excitatory synapse.